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Biomedical subjects

Dennis Velakoulis

Publications and source records attributed to Dennis Velakoulis.

At least 19 recordsLinked to original sources
PubMed2006

Dysfunction of dorsolateral prefrontal cortex in antipsychotic-naïve schizophreniform psychosis.

Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-naïve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.

Adolescent↗
PubMed2006

The influence of sulcal variability on morphometry of the human anterior cingulate and paracingulate cortex.

Human anterior cingulate (ACC) and paracingulate (PaC) cortices play an important role in cognitive and affective regulation and have been implicated in numerous psychiatric and neurological conditions. The region they comprise displays marked inter-individual variability in sulcal and gyral architecture, and although recent evidence suggests that this variability has functional significance, it is often ignored in automated and region-of-interest (ROI) morphometric investigations. This has lead to confounded interpretation of results and inconsistent findings across a number of studies and in a variety of clinical populations. In this paper, we present a reliable method for parcellating the dorsal, ventral, and subcallosal ACC and PaC that accounts for individual variation in the local cortical folding pattern. We also investigated the effect of one well characterized morphological variation, the incidence of the paracingulate sulcus (PCS), on regional volumes in 24 (12 male, 12 female) healthy participants. The presence of a PCS was shown to affect both ACC and PaC volumes, such that it was associated with an 88% increase in paracingulate cortex and a concomitant 39% decrease in cingulate cortex. These findings illustrate the potential confounds inherent in morphometric approaches that ignore or attempt to minimize inter-individual variations in sulcal and gyral anatomy and underscore the need to consider this variability when attempting to understand disease processes or characterize brain structure-function relationships.

Adult↗
PubMed2006

Evaluating brain activity in obsessive-compulsive disorder: preliminary insights from a multivariate analysis.

Obsessive-compulsive disorder (OCD) has been linked to a dysfunction of brain corticostriatal networks, although functional imaging studies of OCD rarely apply network-sensitive analysis methods. In this study, we compared a univariate and a multivariate analysis of PET data in OCD patients and healthy subjects; the latter approach was considered more suitable for characterizing functional networks of brain activity. Although both methods suggested there was abnormal corticostriatal activity in OCD patients, the nature, extent and magnitude of this activity was clearly enhanced by the multivariate approach. Implications for the analysis of such studies are discussed.

Adult↗
PubMed2006

Morphology of the paracingulate sulcus and executive cognition in schizophrenia.

Previous studies have shown that schizophrenia patients display a left-lateralized reduction in cortical folding of the paracingulate cortex, although the functional significance of this anomaly is unclear. We examined the influence of paracingulate sulcus (PCS) asymmetries on cognitive performance in 37 male schizophrenia patients and 43 male controls. Across both groups, a leftward PCS asymmetry was associated with better spatial working memory performance than either a rightward asymmetric or symmetric folding pattern. This suggests that prior reports of impaired performance on such tasks in schizophrenia may be partly explained by the reduced frequency of a leftward PCS asymmetry in this population.

Adult↗
PubMed2006

Neuropathological, neurogenetic and neuroimaging evidence for white matter pathology in schizophrenia.

A wide range of neuropathological abnormalities have been detected in schizophrenia sufferers, and emerging evidence points to neural substrates of connectivity as having a key role in the development of disease. This article reviews the available evidence for white matter pathology in schizophrenia, and examines its possible role as a substrate of impaired connectivity. Neuropathological data is suggestive of abnormalities in glial structure and function, and myelinated structures have also been implicated. A number of studies, particularly using gene array technology, are pointing towards significant disruption in expression of myelination genes. Magnetic resonance imaging has tended to focus on, and detect, more grey than white matter abnormalities, although non-volumetric techniques are suggestive of changes in the microstructure of white matter in schizophrenia. Myelinated structures are an attractive candidate for an anatomical substrate for disconnectivity, and may act synergistically with synaptic changes to result in functional disconnectivity although the relationship between white and grey matter changes in the illness remains unclear.

Animals↗
PubMed2006

Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals.

CONTEXT: Magnetic resonance imaging studies have identified hippocampal volume reductions in schizophrenia and amygdala volume enlargements in bipolar disorder, suggesting different medial temporal lobe abnormalities in these conditions. These studies have been limited by small samples and the absence of patients early in the course of illness. OBJECTIVE: To investigate hippocampal and amygdala volumes in a large sample of patients with chronic schizophrenia, patients with first-episode psychosis, and patients at ultra-high risk for psychosis compared with control subjects. DESIGN: Cross-sectional comparison between patient groups and controls. SETTING: Individuals with chronic schizophrenia were recruited from a mental health rehabilitation service, and individuals with first-episode psychosis and ultra-high risk were recruited from the ORYGEN Youth Health Service. Control subjects were recruited from the community. PARTICIPANTS: The study population of 473 individuals included 89 with chronic schizophrenia, 162 with first-episode psychosis, 135 at ultra-high risk for psychosis (of whom 39 subsequently developed a psychotic illness), and 87 controls. MAIN OUTCOME MEASURES: Hippocampal, amygdala, whole-brain, and intracranial volumes were estimated on high-resolution magnetic resonance images and compared across groups, including first-episode subgroups. We used 1- and 2-way analysis of variance designs to compare hippocampal and amygdala volumes across groups, correcting for intracranial volume and covarying for age and sex. We investigated the effects of medication and illness duration on structural volumes. RESULTS: Patients with chronic schizophrenia displayed bilateral hippocampal volume reduction. Patients with first-episode schizophrenia but not schizophreniform psychosis displayed left hippocampal volume reduction. The remaining first-episode subgroups had normal hippocampal volumes compared with controls. Amygdala volume enlargement was identified only in first-episode patients with nonschizophrenic psychoses. Patients at ultra-high risk for psychosis had normal baseline hippocampal and amygdala volumes whether or not they subsequently developed a psychotic illness. Structural volumes did not differ between patients taking atypical vs typical antipsychotic medications, and they remained unchanged when patients treated with lithium were excluded from the analysis. CONCLUSIONS: Medial temporal structural changes are not seen until after the onset of a psychotic illness, and the pattern of structural change differs according to the type of psychosis. These findings have important implications for future neurobiological studies of psychotic disorders and emphasize the importance of longitudinal studies examining patients before and after the onset of a psychotic illness.

Adolescent↗
PubMed2006

Prediction of functional outcome 18 months after a first psychotic episode: a proton magnetic resonance spectroscopy study.

CONTEXT: Recent magnetic resonance imaging studies have attempted to relate volumetric brain measurements in early schizophrenia to clinical and functional outcome some years later. These studies have generally been negative, perhaps because gray and white matter volumes inaccurately assess the underlying dysfunction that might be predictive of outcome. OBJECTIVE: To investigate the predictive value of frontal and temporal spectroscopy measures for outcome in patients with first-episode psychoses. DESIGN: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These data were used to predict outcome at 18 months after admission, as assessed by a systematic medical record audit. SETTING: Early psychosis clinic. PARTICIPANTS: Forty-six patients with first-episode psychosis. MAIN OUTCOME MEASURES: We used regression models that included age at imaging and duration of untreated psychosis to predict outcome scores on the Global Assessment of Functioning Scale, Clinical Global Impression scales, and Social and Occupational Functional Assessment Scale, as well as the number of admissions during the treatment period. We then further considered the contributions of premorbid function and baseline level of negative symptoms. RESULTS: The only spectroscopic predictor of outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this variable were related to poorer outcome on all measures. In addition, the frontal NAA/Cr ratio explained 17% to 30% of the variance in outcome. CONCLUSIONS: Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis; rather, it is an early marker of poor prognosis across the first years of illness. The extent to which this can be used to guide treatment and whether it predicts outcome some years after first presentation are questions for further research.

Adult↗
PubMed2006

Neuropsychiatry of complex visual hallucinations.

OBJECTIVE: To describe the phenomenology and pathophysiology of complex visual hallucinations (CVH) in various organic states, in particular Charles Bonnet syndrome and peduncular hallucinosis. METHOD: Three cases of CVH in the setting of pontine infarction, thalamic infarction and temporoparietal epileptiform activity are presented and the available psychiatric, neurological and biological literature on the structures of the central nervous system involved in producing hallucinatory states is reviewed. RESULTS: Complex visual hallucinations can arise from a variety of processes involving the retinogeniculocalcarine tract, or ascending brainstem modulatory structures. The cortical activity responsible for hallucinations results from altered or reduced input into these regions, or a loss of ascending inhibition of their afferent pathways. CONCLUSIONS: A significant degree of overlaps exists between the concepts of Charles Bonnet syndrome and peduncular hallucinosis. The fluidity of these eponymous syndromes reduces their validity and meaning, and may result in an inappropriate attribution of the underlying pathology. An understanding of how differing pathologies may produce CVH allows for the appropriate tailoring of treatment, depending on the site and nature of the lesion and content of perceptual disturbance.

Adult↗
PubMed2006

Chronic mental illness and community treatment resistance.

OBJECTIVES: The movement from institutional to community care has been a key component of national mental health reform in Australia. In Victoria, where a model of community care has been fully implemented, a specialized forensic hospital is the sole remaining stand-alone psychiatric inpatient facility and access to long-term inpatient beds is severely limited. Clinical experience suggests that some high-needs patients are not well serviced by this structure. These patients are placing an increasing burden on a wide range of community services outside mental health. This paper aims to define more clearly this patient group, explore the limitations of their management and outline potential pathways for service development. CONCLUSIONS: A population of complex patients with chronic mental illness are not effectively contained within a 'good enough' community-based mental health system. Active debate is required regarding the community's willingness to tolerate the risks and challenges that arise from the current approach. A collaborative care model involving case-based and incentive funding in combination with community-integrated complex care units may improve the care of these patients.

Adult↗
PubMed2006

A case of schizophrenia with complete agenesis of the corpus callosum.

OBJECTIVE: To describe the case of a person with schizophrenia and agenesis of the corpus callosum. CONCLUSION: A 24-year-old Caucasian woman with schizophrenia was incidentally found to have complete agenesis of the corpus callosum. A comprehensive neuropsychiatric assessment allowed management to be specifically tailored to the patient's unique clinical profile.

Adult↗
PubMed2006

Recovery of cognitive function in neuropsychiatric Langerhan's cell histiocytosis.

Langerhan's cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by neurological and cognitive decline. The authors here report a case of a childhood LCH sufferer who made a significant recovery of neuropsychological function in the absence of motor recovery in late adolescence. This differential recovery of motor and cognitive functioning may relate to the interaction between LCH and childhood and adolescent neurodevelopmental processes.

Adult↗
PubMed2006

Reversible dementia with psychosis: Hashimoto's encephalopathy.

A case of presumed Hashimoto's encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative.

Aged↗
PubMed2006

The neuropsychiatry of Niemann-Pick type C disease in adulthood.

Psychotic symptoms occur in a variety of medical and neurological conditions. The authors describe three young men with a variant form of Niemann-Pick type C disease, a neurodegenerative disorder related to abnormal intracellular cholesterol metabolism, who presented with psychosis in early adulthood. Two patients were treated for schizophrenia for many years prior to a diagnosis of Niemann-Pick type C. The cases presented in this article illustrate the role of changes in both white and gray matter structures in psychosis, and, like the assessments of other neurodevelopmental disorders that predispose toward psychotic presentations, shed light on the underlying pathophysiology of major mental disorders.

Adult↗
PubMed2005

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis.

BACKGROUND: We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. METHODS: Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. RESULTS: Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (-6%; p = .032). CONCLUSIONS: The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

Adolescent↗
PubMed2005

Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia.

The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an "early neurodevelopmental" lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre- or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre- and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness. However, the pathological processes underlying such progressive changes during "late neurodevelopment" remain unclear but may reflect anomalies of synaptic plasticity, abnormal brain maturation, the adverse effects of stress, or other environmental factors. In this context, the features of schizophrenia, including the neuropsychological deficits and behavioral manifestations, can be understood as direct effects of these multiple pathological processes at various neurodevelopmental stages, including genetic and nongenetic etiological factors.

Brain↗
PubMed2005

Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness.

BACKGROUND: While structural brain imaging abnormalities have been identified in schizophrenia and related disorders, it is unclear when they arise. Some appear to predate the illness and may be genetic in origin, while others are associated with the onset of the disorder. METHODS: We examined the hippocampal volumes and anterior cingulate morphology from the MRI scans of 79 male subjects at ultra-high-risk (UHR) for developing psychosis, 35 of whom had a family history of schizophrenia, and compared them with 49 healthy male volunteers. RESULTS: Analysis of covariance demonstrated that left hippocampal volumes were significantly smaller in the UHR group without a family history of schizophrenia, when compared to the UHR group with such history. A similar pattern was found for the left anterior cingulate region, both in terms of reduced paracingulate folding and cingulate sulcus interruptions, although this did not reach significance. CONCLUSIONS: We found that a family history of schizophrenia was not associated with a greater degree of structural brain abnormalities in an ultra-high-risk group, and in fact it was those UHR patients without such history who displayed greater abnormalities, although this only reached significance for the left hippocampus. Thus, it appears that the mechanisms that result in gross morphological anomalies in the hippocampus and anterior cingulate in psychosis are driven more by environmental than genetic factors.

Adult↗
PubMed2005

A manual and automated MRI study of anterior cingulate and orbito-frontal cortices, and caudate nucleus in obsessive-compulsive disorder: comparison with healthy controls and patients with schizophrenia.

Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with samples of healthy (HC) and psychiatric (schizophrenia; SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.

Adult↗